Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV004799596 | SCV001468811 | uncertain significance | Dilated cardiomyopathy 1G; Hypertrophic cardiomyopathy 9 | 2019-05-30 | criteria provided, single submitter | clinical testing | The inherited c.12026A>G (p.Tyr4009Cys) variant identified substitutes a highly conserved Tyrosine for Cysteine at amino acid 4009/35992 (coding exon 48/363). It is found with low frequency in gnomAD (3 heterozygotes, 0 homozygotes; allele frequency: 1.210e-5) and ExAC (3 heterozygotes, 0 homozygotes; allele frequency: 2.495e-5), suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms predict this variant is Deleterious (Provean; score: -6.07) and Damaging (SIFT; score:0.001) to the function of the canonical transcript. The variant is absent from ClinVar, and to our current knowledge has not been identified in affected individuals in the literature. Given the lack of compelling evidence for the pathogenicity of the inherited c.12026A>G (p.Tyr4009Cys) variant identified here, it is reported as a Variant of Uncertain Significance. |
Prevention |
RCV004531055 | SCV004120920 | uncertain significance | TTN-related disorder | 2024-01-30 | no assertion criteria provided | clinical testing | The TTN c.12026A>G variant is predicted to result in the amino acid substitution p.Tyr4009Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |